The research program is focused on the neural and molecular mechanisms underlying information storage. Previously Dr. Byrne found that a classical conditioning protocol applied directly to individual tail sensory neurons results in an associative modification of the monosynaptic connections to motor neurons. Sensory neurons receiving a conditioned stimulus (CS, intracellular activation of the sensory neuron) immediately before the unconditioned stimulus (US, tail shock) show significantly more synaptic facilitation than sensory neurons exposed to the US alone or to unpaired CS and US applications. An analog of the classical conditioning paradigm produces a selective amplification of the cAMP content of isolated sensory neuron clusters. These results indicate that a pairing- specific enhancement of cAMP levels may be a biochemical mechanism for associative learning. Experiments proposed here are designed to extend these analyses. Specifically, Dr. Byrne will examine 1) whether Ca2+ serves as the signal for the induction of the associative change, 2) whether cAMP levels in the sensory neurons are increased during simple forms of learning such as sensitization and classical conditioning, 3) the contribution of spike broadening in the sensory neurons to synaptic facilitation and behavioral modification, 4) the properties of the neural circuit elements mediating the reflex and effects of the US, and 5) the coordination and modulation of synergistic defensive responses triggered by tail stimulation. Continued analysis of this system promises to yield much additional information concerning the cellular mechanisms underlying associative and nonassociative learning. The award will foster Dr. Byrne's research development and professional growth. It will allow him to expand his research program by hiring a junior colleague. It will give Dr. Byrne the flexibility to plan interludes to develop new areas of expertise through collaboration and visits with other scientists in the field.